Distribution of [Leu31,Pro34]NPY-sensitive, BIBP3226-insensitive [125I]PYY(3-36) binding sites in rat brain: possible relationship to Y5 NPY receptors.
Recently, using molecular cloning approaches, three new neuropeptide Y (NPY)/peptide YY (PYY) receptors have been described in rodent brain, with pharmacological profiles that differ from the three previously described Y1, Y2 and Y3 NPY receptors and the Y4 pancreatic polypeptide- (PP-) preferring receptor. Two of these new receptors are spice variants and are called Y5 receptors, whilst a third receptor has been called Y6 and has been suggested to be expressed only in the mouse. In the absence of a totally selective Y5 and/or Y6 radioligands, we have examined [125I]PYY(3-36) binding, which binds Y2 and Y5/Y6 receptors, using homogenate assays and quantitative receptor autoradiography to study the distribution of the three newly discovered Y5/Y6 receptors by masking binding to Y1 receptors with high concentrations of the non-peptidergic selective Y1 antagonist, BIBP3226, and using either [Leu31,Pro34]NPY or human PP to mask binding to Y5 and Y6 receptors, leaving binding to Y2 receptors. Using this approach, [125I]PYY(3-36) labels a small population of Y1 receptors and a larger population of binding sites that are insensitive to BIBP3226, human PP and [Leu31,Pro34]NPY, presumed to be Y2 receptors. There was also [125I]PYY(3-36) binding to sites sensitive to NPY, human PP and [Leu31,Pro34]NPY, but insensitive to BIBP3226, located in the hypothalamus, amygdala, hippocampus and thalamus. As one of the recently cloned Y5 receptors is synthesized in these regions, as shown by in-situ hybridization techniques, we suggest that the small population of [125I]PYY(3-36) binding sites which are sensitive to human PP and [Leu31,Pro34]NPY, but insensitive to BIBP3226, may represent binding to Y5 receptors. We have been unable, however, to visualize a smaller population of Y6 receptors which are labelled by [125I]PYY3-36 and sensitive to [Leu31,Pro34]NPY, but not to BIBP3226 and human PP, confirming that the murine Y6 receptor does not appear to be expressed in rat brain.
Widdowson
P S
PS
Department of Medicine, University of Liverpool, UK.
Buckingham
R
R
Williams
G
G
D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001665:Binding Sites; D001667:Binding, Competitive; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D007457:Iodine Radioisotopes; D008297:Male; D009478:Neuropeptide Y / Q000031:analogs & derivatives* / Q000494:pharmacology; D010446:Peptide Fragments; D019894:Peptide YY / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D017476:Receptors, Neuropeptide Y / Q000037:antagonists & inhibitors*
C092926:BIBP 3226; D007457:Iodine Radioisotopes; D009478:Neuropeptide Y; D010446:Peptide Fragments; D017476:Receptors, Neuropeptide Y; D019894:Peptide YY; C061785:peptide YY (3-36); C062259:neuropeptide Y, Leu(31)-Pro(34)-; D001120:Arginine